High-frequency (80–500Hz) oscillations and epileptogenesis in temporal lobe epilepsy

Abstract

High-frequency oscillations (HFOs), termed ripples and fast ripples , are recorded in the EEG of epileptic patients and in animal epilepsy models; HFOs are thought to reect pathological activity and seizure onset zones. Here, we analyzed the temporal and spatial evolution of interictal spikes with and without HFOs in the rat pilocarpine model of temporal lobe epilepsy. Depth electrode recordings from dentate gyrus (DG), CA3 region, subiculum and entorhinal cortex (EC), were obtained from rats between the 4th and 15th day after a status epilepticus (SE) induced by i.p. injection of pilocarpine. The first seizure occurred 6.1±2.5 days after SE (n=7 rats). Five of 7 animals exhibited interictal spikes that co-occurred with fast ripples accounting for 4.9±4.6% of all analyzed interictal spikes (n=12,886) while all rats showed interictal spikes co-occurring with ripples, accounting for 14.3±3.4% of all events. Increased rates of interictal spikes without HFOs in the EC predicted upcoming seizures on the following day, while rates of interictal spikes with fast ripples in CA3 reflected periods of high seizure occurrence. Finally, interictal spikes co-occurring with ripples did not show any specific relation to seizure occurrence. Our findings identify different temporal and spatial developmental patterns for the rates of interictal spikes with or without HFOs in relation with seizure occurrence. These distinct categories of interictal spikes point at dynamic processes that should bring neuronal networks close to seizure generation.

Mechanisms of physiological and epileptic HFO generation

“…These fast ripples or pHFOs provided a marker for epileptogenesis because they were seen selectively in the injected hippocampi of those rats that would go on to develop chronic epilepsy. Long-term recordings in the pilocarpine model have also shown a tight link between regions that generate spontaneous seizures and fast ripple activity (Lévesque et al, 2011). Increased fast ripple rates in the seizure onset zone were more specifically indicative of periods of high susceptibility to seizure occurrence, suggesting a role of HFOs in epileptogenesis.…”

“…Perhaps the most commonly used chronic models of TLE rely on a period of status epilepticus lasting over 40 min (typically 1-2 h) with may be induced, in rat or in some cases in mouse, by one of kainic acid (KA, intrahippocampal or intraperitoneal) (Ben-Ari et al, 1980;Cavalheiro et al, 1982;Dudek et al, 2006), pilocarpine (intraperitoneal) (Cavalheiro et al, 2006;Curia et al, 2008) or electrical stimulation (intracerebral) (Gorter et al, 2001;Walker et al, 1999). In each of these models the induced status epilepticus is followed by a latent period of days to a couple of weeks before spontaneous seizures start, and then recur for the rest of the lifetime of the animal (Bortel et al, 2010;Lévesque et al, 2011;Williams et al, 2009). The latent period is not silent, as originally thought, but rather is characterized by progressive electrographic abnormalities that culminate in seizures (Bortel et al, 2010;Bragin et al, 1999b;White et al, 2010).…”

Generation of physiological and pathological high frequency oscillations: the role of perisomatic inhibition in sharp-wave ripple and interictal spike generation

“…These irregularly-occurring, transient, high activity events (THAEs) carry distinct forms of superimposed high frequency oscillations (HFOs) [1 -4]. Many phenomena are lumped under HFOs [5] including high-frequency gamma (80-1 00Hz), epsilon [6], ripples ) that can be a part of physiological and pathological events [7], and fast ripples (fRIPs, 200-800Hz) that appear exclusively in pathological cases [8-1 0] but often alternate with ripples in the physiological range within the same transient. Sharp-wave-ripple complexes (SWR) are recurring physiological transients [3,11 ] that are essential for memory consolidation [1 2-1 4] and are ornamented with ripple oscillations in the 1 40-200 Hz range [1 5].…”

Two Seizure-Onset Types Reveal Specific Patterns of High-Frequency Oscillations in a Model of Temporal Lobe Epilepsy

“…HFOs occur in limbic structures such as the hippocampus and entorhinal cortex, as well as in the neocortex, and they are thought to reflect the activity of dysfunctional neural networks that underlie and sustain epileptogenesis (Bragin et al, 2004;Jacobs et al, 2009Jacobs et al, , 2010Ibarz et al, 2010;Jiruska et al, 2010a;Wu et al, 2010;Lévesque et al, 2011). HFOs are also better markers than interictal spikes to identify the seizure-onset zone, independently of the underlying pathology (Jacobs et al, 2008(Jacobs et al, , 2009Crépon et al, 2010).…”